Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7
Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7
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DOI：
10.1073/pnas.0511094103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Fauci, AS
中科院分区：
文献类型：
--
作者：
Malaspina, A;Moir, S;Fauci, AS
HIV 疾病的进展与大量 B 细胞缺陷的出现有关。我们在此描述了在患有进展性HIV疾病的个体的外周血中过度代表的未成熟/过渡B细胞群。这些 B 细胞通过 CD10 的表达进行鉴定，对 B 细胞受体触发的增殖没有反应，并具有表型和 Ig 多样性谱，证实它们处于分化的不成熟/过渡阶段。与未成熟状态一致，它们对 B 细胞受体触发的增殖缺乏可被 CD40 配体逆转，但不能被 B 细胞激活因子逆转。最后，B 细胞上的 CD10 表达水平与 IL-7 的血清水平直接相关，表明 IL-7 水平的增加通过对淋巴细胞减少的稳态效应直接或间接调节人 B 细胞的成熟。总而言之，这些数据提供了对人类 B 细胞发育以及晚期 HIV 疾病中 B 细胞功能障碍的深入了解，这些功能可能与 IL-7 依赖性稳态事件有关。
Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature/transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10, were unresponsive by proliferation to B cell receptor triggering and possessed a phenotype and an Ig diversity profile that confirmed their immature/transitional stage of differentiation. Consistent with an immature status, their lack of proliferation to B cell receptor triggering was reversed with CD40 ligand, but not B cell activation factor. Finally, levels of CD10 expression on B cells were directly correlated with serum levels of IL-7, suggesting that increased levels of IL-7 modulate human B cell maturation either directly or indirectly by means of a homeostatic effect on lymphopenia. Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events.